title: Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage.
abstract: Matrix metalloproteinases (MMP) consisting of at least 16 different molecules are thought to be involved in the degradation of extracellular matrix (ECM) macromolecules under various pathologic conditions. Among them, MMP-7 (matrilysin) is unique in that it has high specific activity against various ECM components such as cartilage proteoglycan. In the present study, we examined the expression and tissue localization of MMP-7 in articular cartilages of human osteoarthritis (OA). Immunohistochemistry using a monoclonal antibody specific to MMP-7 demonstrated that the proteinase is localized to the OA chondrocytes mainly in the superficial and transitional zones in 92% of the OA cases examined (36 of 39 cases). On average, approximately 30% of the total chondrocytes (29.1%+/-30.2%) were immunostained in the positive OA cartilage samples. In contrast, MMP-7 staining was found in 8% of the normal cartilage cases (1 of 12 cases), and only a few chondrocytes (0.15%+/-0.67%) in the superficial zone were immunostained. There was a linear correlation between degree (%) of the immunostained chondrocytes and Mankin scores (rho [rho] = 0.84). Immunoblot analysis of the culture media from the cartilage explants demonstrated MMP-7 in 65% of the OA cases (15 of 23 cases) and 8% of the normal specimens (1 of 12 cases). Reverse transcription-PCR demonstrated the specific amplicon in 68% of the OA cartilage cases (17 of 25 cases), whereas only 18% of the control (2 of 11 cases) amplified the product. In situ hybridization revealed that the chondrocytes in OA cartilage express MMP-7 mRNA. MMP-7 gene expression in cultured OA chondrocytes was enhanced by the treatment with interleukin-1alpha and/or tumor necrosis factor-alpha. These data demonstrate for the first time that MMP-7 is overexpressed in human OA cartilage and suggest that cytokine-induced MMP-7 may play an important role in the degradation of ECM macromolecules in the OA cartilage.
authors.affiliation: Department of Molecular Immunology and Pathology, Cancer Research Institute, Kanazawa University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: I
authors.initials: I
authors.lastname: Azumano
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000201:enzymology*; D004792:Enzyme Precursors / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004792:Enzyme Precursors; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases; C099583:promatrilysin; D020783:Matrix Metalloproteinase 7